Issues
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Cover Image
Cover Image
Increased understanding of the pancreatic ductal adenocarcinoma (PDAC) immune microenvironment has the potential to improve immunotherapeutic strategies for this intractable disease. Using machine learning to analyze a single-cell, spatial, and highly multiplexed proteomic dataset, Blise et al. show that neoadjuvant anti-CD40 immunotherapy reduces expression of biomarkers associated with T-cell exhaustion in the PDAC microenvironment. Improved disease-free survival among anti-CD40–treated patients is associated with the presence of cellular neighborhoods comprising T cells exhibiting increased antigen-experience, proliferative function, and cytotoxicity. The data highlight the power of machine learning to reveal cellular and spatial changes induced by immunotherapy, which could lead to the identification of biomarkers of response and new therapeutic strategies. Read more in this issue on page 544. Original image from Fig. 3D. Artwork by Lewis Long. - PDF Icon PDF LinkTable of Contents
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Cancer Immunology Research
Cancer Immunology Research, launched in 2013 with Glenn Dranoff as founding Editor-in-Chief, is published by the AACR. The Journal illuminates the interplay between tumors and the immune system, with Robert D. Schreiber and Philip D. Greenberg serving as the Editors-in-Chief.
Table of Contents
What We're Reading
In the Spotlight
Research Articles
Chronic Stress Exacerbates the Immunosuppressive Microenvironment and Progression of Gliomas by Reducing Secretion of CCL3
How chronic stress impacts glioma progression is unclear. The authors show it inhibits CCL3 secretion, exacerbating formation of an immunosuppressive microenvironment and thereby promoting glioma progression. CCL3 administration may be a new immunotherapy for glioma patients with depression.
Tsyn-Seq: a T-cell Synapse–Based Antigen Identification Platform
Genome-wide identification of antigens targeted by individual TCRs can be challenging. The authors developed a new platform (Tsyn-seq) that allows for traditional cDNA library–based screening of antigen targets but is adapted for both increased ease and throughput.
Machine Learning Links T-cell Function and Spatial Localization to Neoadjuvant Immunotherapy and Clinical Outcome in Pancreatic Cancer
PDAC is largely refractory to immunotherapy. The authors use machine learning models to disentangle the complex PDAC TME, revealing effector T cells are increased after neoadjuvant anti-CD40 immunotherapy, including in immune aggregate sites that correspond with improved DFS.
High-Dimensional Analyses Reveal IL15 Enhances Activation of Sipuleucel-T Lymphocyte Subsets and Reverses Immunoresistance
Sip-T is FDA approved to treat mCRPC. Using CyTOF, the authors show a lymphoid predominance in sip-T and provide evidence that IL15 treatment enhances sip-T antitumor function, providing rationale for combining IL15 or IL15 agonists with sip-T.
PVRL2 Suppresses Antitumor Immunity through PVRIG- and TIGIT-independent Pathways
The authors uncover a central role for PVRL2 in suppressing antitumor immune responses, largely independent of its receptor PVRIG. Combined PVRL2 and TIGIT targeting results in a near-complete block in tumor growth, suggesting a novel therapeutic approach.
ILT2 and ILT4 Drive Myeloid Suppression via Both Overlapping and Distinct Mechanisms
ILT2 and ILT4 play a role myeloid-cell inhibition in the tumor microenvironment. The authors show that combined blockade of ILT2 and ILT4 is required to induce optimal myeloid-cell reprogramming and activation in a solid tumor microenvironment.
ANXA3-Rich Exosomes Derived from Tumor-Associated Macrophages Regulate Ferroptosis and Lymphatic Metastasis of Laryngeal Squamous Cell Carcinoma
The mechanisms by which TAM-derived exosomes influence tumor progression remain unclear. The authors show that ANXA3 promotes M2-like polarization of macrophages and ANXA3-rich exosomes secreted by TAMs regulate ferroptosis and lymphatic metastasis in LSCC.
The TOPK Inhibitor HI-TOPK-032 Enhances CAR T-cell Therapy of Hepatocellular Carcinoma by Upregulating Memory T Cells
The effects of CAR T-cell therapy on solid tumors remain limited. The authors show that treatment with a TOPK-specific inhibitor enhances GPC3-targeted CAR T-cell therapy in HCC tumor models by increasing central memory CD8+ CAR T cells.
Journal Archive
Cancer Immunology Research
(2013-Present)Published monthly since 2013.
(ISSN 2326-6066)
Cancer Immunity
(2001-2013; volumes 1-13)Published periodically from 2001-2013.
(EISSN 1424-9634)
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